As we shift HIV-research focus towards secondary complications and aging in the modern therapy era, mental, behavior and cognitive health are critical domains for study. HIV-infected individuals are at high risk for depression, substance abuse and cognitive impairments, all of which can be exacerbated by the social stresses that gay and HIV-infected populations often endure. Many of these problems are also problems of aging and the U.S. HIV-infected population is rapidly approaching a median age of 50 years. These issues can only rise in importance as age and HIV-related factors drive up the prevalence of depression and cognitive impairment. We propose to use a comprehensive approach to understand the complex relationships between psychosocial factors and long term trends in depression and cognitive function. Using novel statistical approaches and data from the Multicenter AIDS Cohort Study, a well-described data source with many under- utilized psychosocial variables and over 25 years of under-explored depressive symptom and neuropsychological (NP) function history, we will elucidate the pathways leading from life-course social stressors through depression to NP decline by: 1. Elucidating the longitudinal relationship between depressive symptoms and NP function tests/self- perceived memory among HIV-infected men. 2. Examining complex interrelations between NP function tests/self-perceived memory, depressive symptoms, substance abuse, social stressors (internalized homophobia, gay victimization), social support and connectedness, HIV disease indicators (viral load, CD4 cell count) and race. 3. Developing methods for identifying and characterizing distinctive patterns of longitudinal depressive symptom and NP outcome data in HIV-infected and -uninfected men who have sex with men (MSM) and describe how treated HIV infection influences these trajectories. Depression is a treatable condition. Disrupting a long-term pattern of chronic or cyclic depression may provide more than just improved quality of life; such an intervention may also prevent, halt or even reverse cognitive function decline. Understanding the nature of the relationship and the myriad pathways between an HIV-infected person's history of depression and their NP functional trajectory is an important first step towards devising an effective screening and intervention program.